Simon Silver

University of Illinois at Chicago | UIC · Department of Microbiology and Immunology (Chicago)

Objective Hyperglycemia leads to lipid peroxidation, producing 4‐hydroxynonenal (HNE) adducts which correlate with the production of amyloid-beta (Aβ), one of the hallmarks of Alzheimer's disease (AD). This study is to investigate the interactions of Aβ, HNE adducts and responding autoantibodies during the pathogenesis from hyperglycemia to AD. Me...

Patents for microbiology and biotechnology are generally for a process (for example DNA cloning; Cohen and Boyer 1980; and polymerase chain reaction, PCR; Mullis 1987) and not for the microbe itself. The patent for oil degrading bacteria (Chakrabarty 1981) was different in that it covered the modified microbial cell itself, a Pseudomonas strain wit...

Scientific journals have virtually disappeared as subscription-based familiar paper copies. These have been replaced by article by article access on internet sites (either subscription based paid for by libraries in multi-journal often million dollar 'Big Deal' packages, or by author prepayments of thousand dollars 'article processing fees' (Omary...

Sixty-five spore-forming mercury-resistant bacteria were isolated from natural environments worldwide in order to understand the acquisition of additional genes by and dissemination of mercury resistance transposons across related Bacilli genera by horizontal gene movement. PCR amplification using a single primer complementary to the inverted repea...

Researchers studying both cellular and viral disease agents in the laboratory have become infected since the early days of microbiology 150 years ago. However, in the early 21st century, new concerns about bioweapons being used to generate terror and also with a series of newly emerging or newly understood disease-causing microbes have resulted in...

identification of anthrax spores (by proteomic analysis), and to determine their precise origin (by means of DNA genomic polymorphisms). The draft genome sequences of 94 environmental Bacillus cereus sensu lato strains were deposited in GenBank (1 )t o facilitate the identification of the closely related subspecies B. cereus, Bacillus anthracis, Ba...

Microbiology has experienced examples of highly-productive researchers who have gone beyond just interpreting their experimental results with hypotheses and published nonsense that was readily recognized as such by readers. Although the most-discussed cases of this pathology come from physics, studies of single celled microbes, virology, and immuno...

This review gives a comprehensive overview of the widespread use and toxicity of silver compounds in many biological applications. Moreover, the bacterial silver resistance mechanisms and their spread in the environment are discussed. This study shows that it is important to understand in detail how silver and silver nanoparticles exert their toxic...

Agrobacterium albertimagni strain AOL15 is an alphaproteobacterium isolated from arsenite-oxidizing biofilms whose draft genome contains 5.1 Mb in 55 contigs with 61.2% GC content and includes a 21-gene arsenic gene island. This is the first available genome for this species and the second Agrobacterium arsenic gene island.

Achromobacter piechaudii strain HLE is a betaproteobacterium (previously known as Alcaligenes faecalis) that was an early isolate with arsenite oxidase activity. This draft genome of 6.89 Mb is the second available genome for this species in the opportunistic pathogen Alcaligenaceae family.

Alcaligenes faecalis subsp. faecalis NCIB 8687, the betaproteobacterium from which arsenite oxidase had its structure solved and the first “arsenate gene island” identified, provided a draft genome of 3.9 Mb in 186 contigs (with the largest 15 comprising 90% of the total) for this opportunistic pathogen species.

Halomonas strain GFAJ-1 was reported in Science magazine to be a remarkable microbe for which there was “arsenate in macromolecules that normally contain phosphate, most notably nucleic acids.” The draft genome of the bacterium was determined (NCBI accession numbers AHBC01000001 through AHBC01000103). It appears to be a typical gamma proteobacteriu...

The first observation of bacterial oxidation of arsenite to arsenate was described in 1918 (5) but it was only in 1992 that the first arsenite oxidase was isolated (1).…

Understanding of BioMetals developed basically from a starting point about 60 years ago to current mechanistic understanding of the biological behavior of many metal ions from protein structural and functional studies. Figure 1 shows a Biochemical Periodic Table, element by element, with requirements, roles and biochemistry of the specific ions ind...

The recent online report in Science ( ⇓ ; http://www.sciencexpress.org ) that a newly isolated bacterial strain can apparently replace phosphate with arsenate in cellular constituents such as DNA and RNA either (1) wonderfully expands our imaginations as to how living cells might function (as the authors and the sponsoring government agency, the US...

Essentially all bacteria with 2000 or more genes have genes for toxic metal ion resistances that include those for Ag+, AsO2−, AsO43−, Cd2+Cd2+, Co2+Co2+, CrO42−, Cu2+Cu2+, Hg2+Hg2+, Ni2+Ni2+, Pb2+Pb2+, TeO32−, Tl+Tl+, and Zn2+Zn2+. The largest group of resistance systems functions by energy-dependent efflux of toxic ions. Others involve enzymatic...

Although this series of ten reports focuses on themicrobiology of a single bacterium namely the beta-proteobacterium Cupriavidus metallidurans CH34,this volume is of general interest for several reasons.Firstly, this unusual multiple toxic metal ion-resistantbacterium has been a model for how microbes handlesuch toxic metal (loids) from the time of...

The mercury resistance module of Bacillus transposon TnMERI1 is regulated by three operator/promoter regions (O/P merB3, O/P merR1, and O/P merR2) and two regulatory proteins (MerR1 and MerR2) encoded by the module itself. To clarify the roles of MerR1 and MerR2 in the regulatory mechanism, both proteins were overexpressed and purified. MerR1 bound...

Without Abstract

Mercury has no beneficial biological role, and is highly toxic to all forms of life. Bacteria are involved in the global environmental cycling of mercury, both by reducing Hg2+ to metallic Hg0, which is less soluble in aqueous systems and therefore less bioavailable, and by oxidizing and methylating Hg species, and in the process making Hg more bio...

This review concerns the question “What is out there?,” about which humankind has speculated since we learned to ask. Is there life elsewhere in the universe? Can we can recognize it? And how did it (and life on earth) arise? These questions are fundamentally microbial. They promise to remain unanswered for the next few years at least. These two bo...

The merC gene from Acidithiobacillus ferrooxidans functions as a mercury uptake pump. MerC protein localizes in the cytoplasmic membrane of plant cells. When Arabidopsis thaliana and tobacco plants were transformed with the merC gene under the control of the Cauliflower mosaic virus 35S promoter, the resulting overexpression of merC rendered the ho...

The frequent abundance of arsenic in the environment has guided the evolution of enzymes for the reduction of arsenate. The arsenate reductases (ArsC) from different sources have unrelated sequences and structural folds, and can be divided into different classes on the basis of their structures, reduction mechanisms and the locations of catalytic c...

Acidithiobacillus ferrooxidans is a chemolithoautotrophic bacterium that uses iron or sulfur as an energy and electron source. Bioinformatic analysis of the A. ferrooxidans draft genome sequence was used to identify putative genes and potential metabolic pathways involved in CO2 fixation, 2P-glycolate detoxification, carboxysome formation and glyco...

Acidithiobacillus ferrooxidans is a well known acidophilic, chemolithoautotrophic, Gram negative, bacterium involved in bioleaching and acid mine drainage. In aerobic conditions, it gains energy mainly from the oxidation of ferrous iron and/or reduced sulfur compounds present in ores. After initial oxidation of the substrate, electrons from ferrous...

Silver products have been used for thousands of years for their beneficial effects, often for hygiene and in more recent years as antimicrobials on wounds from burns, trauma, and diabetic ulcers. Silver sulfadiazine creams (Silvazine and Flamazine) are topical ointments that are marketed globally. In recent years, a range of wound dressings with sl...

Essentially all bacteria have genes for toxic metal ion resistances and these include those for Ag+, AsO2-, AsO4(3-), Cd2+ Co2+, CrO4(2-), Cu2+, Hg2+, Ni2+, Pb2+, TeO3(2-), Tl+ and Zn2+. The largest group of resistance systems functions by energy-dependent efflux of toxic ions. Fewer involve enzymatic transformations (oxidation, reduction, methylat...

Topological analysis with a phoA gene fusion suggested that Acidithiobacillus ferrooxidans MerC, a mercury transporter, has two periplasmic loops and four transmembrane domains. Cys-23 and Cys-26 of the protein were involved in Hg(2+)-recognition/uptake, but Cys-132 and Cys-137 were not. Escherichia coli cells producing the MerC were hypersensitive...

The human use of toxic heavy metals is here to stay. In addition to intentional poisoning with arsenic (40) (arsenic levels in the hair of Napoleon Bonaparte approached 40 ppm, more than 1,000 times above allowable levels), medical, agri- cultural, and industrial uses of arsenic present major human problems (5, 40, 41). Arsenic catastrophes are occ...

The First Cell arose in the previously pre-biotic world with the coming together of several entities that gave a single vesicle the unique chance to carry out three essential and quite different life processes. These were: (a) to copy informational macromolecules, (b) to carry out specific catalytic functions, and (c) to couple energy from the envi...

Candidate genes have been identified in the almost complete genome sequence of Acidithiobacillus ferrooxidans that are potentially involved in several physiological processes of relevance to the application of this microorganism to biohydrometallurgical processes. Candidates for six of the 10 missing genes in the previously described amino acid bio...

Resistance to silver compounds as determined by bacterial plasmids and genes has been defined by molecular genetics. Silver resistance conferred by the Salmonella plasmid pMGH100 involves nine genes in three transcription units. A sensor/responder (SilRS) two-component transcriptional regulatory system governs synthesis of a periplasmic Ag(I)-bindi...

Thirty mercury-resistant (Hg R) Bacillus strains were isolated from mercury-polluted sediment of Minamata Bay, Japan. Mercury resistance phenotypes were classified into broad-spectrum (resistant to inorganic Hg(2+) and organomercurials) and narrow-spectrum (resistant to inorganic Hg(2+) and sensitive to organomercurials) groups. Polymerase chain re...

Resistance to silver compounds as determined by bacterial plasmids and genes has been defined by molecular genetics. Silver resistance conferred by the Salmonella plasmid pMGH100 involves nine genes in three transcription units. A sensor/responder (SilRS) two-component transcriptional regulatory system governs synthesis of a periplasmic Ag(I)-bindi...

The broad-spectrum mercury resistance transposon, TnMERI1, of Bacillus megaterium strain MB1, contains three proposed operator/promoter (O/P) transcriptional start sites and two regulatory genes (merR1 and merR2). A series of luciferase (lux)-based transcriptional fusion plasmids were studied in Escherichia coli to show that both merR1 and merR2 ge...

Arsenic compounds have been abundant at near toxic levels in the environment since the origin of life. In response, microbes have evolved mechanisms for arsenic resistance and enzymes that oxidize As(III) to As(V) or reduce As(V) to As(III). Formation and degradation of organoarsenicals, for example methylarsenic compounds, occur. There is a global...

Silver compounds are used as antimicrobial agents in medicine and bacteria that develop resistance to silver cations (Ag(+)) pose problems similar to those of antibiotic-resistant bacteria. The first set of Ag(+) resistance genes (sil) was from plasmid pMG101, now assigned to the IncHI incompatibility group. Questions of whether sil genes are uniqu...

Bacterial resistance to toxic heavy metal ions is generally controlled by genes on extrachromosomal resistance (R) factors that also house the genes conferring resistance to antibiotics. These R factors can be mobilized from cell to cell by direct conjugation and thus afford a rapid mechanism for changing a population of microorganisms that is pred...

A mer operon of mercury-resistant Pseudoalteromonas haloplanktis strain M1, isolated from sea water of Minamata Bay, was cloned and analyzed. The mer genes were located in the chromosome and organized as merR-merT-merP-merC-merA-merD, the same order as that in Tn21. However, the orientation of the merR gene is the same as that of other mer genes (o...

A gapped genome sequence of the biomining bacterium Thiobacillus ferrooxidans strain ATCC23270 was assembled from sheared DNA fragments (3.2-times coverage) into 1,912 contigs. A total of 2,712 potential genes (ORFs) were identified in 2.6 Mbp (megabase pairs) of Thiobacillus genomic sequence. Of these genes, 2,159 could be assigned functions by us...

The chromosomal mercury resistance determinant of Bacillus cereus RC607 confers resistance to inorganic mercury and to organomercurials. The order of genes in the completed mercury resistance determinant is operator-promoter 1 (O/P1) merR1 merT open reading frame 3 (ORF3) ORF4 merA O/P2 merR2 merB2 merB1. The previously undetermined 1-kb DNA sequen...

Here we report the genetic and proposed molecular basis for silver resistance in pathogenic microorganisms. The silver resistance determinant from a hospital burn ward Salmonella plasmid contains nine open reading frames, arranged in three measured and divergently transcribed RNAs. The resistance determinant encodes a periplasmic silver-specific bi...

Bacterial resistance to Ag(I) has been reported periodically with isolates from many environments where toxic levels of silver might be expected to occur, but initial reports were limited to the occurrence of resistant bacteria. The availability of silver-resistance conferring DNA sequences now allow genetic and mechanistic studies that had basical...

Silver resistance of sensitive Escherichia coli J53 and resistance plasmid-containing J53(pMG101) was affected by halides in the growth medium. The effects of halides on Ag+ resistance were measured with AgNO3 and silver sulfadiazine, both on agar and in liquid. Low concentrations of chloride made the differences in MICs between sensitive and resis...

Bacterial chromosomes have genes for transport of inorganic nutrient cations (such as NH4+, K+, Mg2+, Co2+, Fe3+, Mn2+, Zn2+ and other trace cations) and oxyanions (such as PO43- and SO42- and less abundant oxyanions). Together these account for sometimes several hundred genes in many bacteria. Bacterial plasmids encode resistance systems for toxic...

The effect of intracellular glutathione on sensitivity to mercuric cations and arsenite anions was studied inEscherichia colimutants that lack glutathione (gshA) with or without an additional mutation affecting the osmotregulant trehalose. The absence of glutathione increased cellular sensitivity to both Hg2+and AsO2−. The double mutant was more se...

“For want of a nail, a shoe is lost; for want of a shoe, the horse is lost; for want of the horse, the rider is lost, for want of the rider the battle is lost; and for want of the battle the Kingdom is lost.” (George Herbert, 1593–1633. Barlet’s Famous Quotes). Clearly iron is important for maintenance of our way of life.

This is the first volume on the role of metal ions in regulating genes to focus not only on toxicity effects of metals but also on the role of metal ions in normal metabolisms, in both prokaryotes and in eukaryotes. This book is a comprehensive treatment of the role of metal ions in gene regulation, and it will be of great utility for those doing b...

Bacterial chromosomes have genes for transport proteins for inorganic nutrient cations and oxyanions, such as NH4+, K+, Mg2+, Co2+, Fe3+, Mn2+, Zn2+ and other trace cations, and PO4(3-), SO4(2-) and less abundant oxyanions. Together these account for perhaps a few hundred genes in many bacteria. Bacterial plasmids encode resistance systems for toxi...

Nature Biotechnology journal featuring biotechnology articles and science research papers of commercial interest in pharmaceutical, medical, and environmental sciences.

Functional evolution of an arsenic resistance operon has been accomplished by DNA shuffling, involving multiple rounds of in vitro recombination and mutation of a pool of related sequences, followed by selection for increased resistance in vivo. Homologous recombination is achieved by random fragmentation of the PCR templates and reassembly by prim...

This chapter discusses the methods to study interactions between metals and microorganisms, and demonstrate the necessity of adopting a multidisciplinary approach to tackle this increasingly important and diverse area of microbiology. The multidisciplinary approach surveyed in the chapter involves microbiology, particularly microbial physiology, ge...

Bacterial plasmids encode resistance systems for toxic metal ions, including Ag+, AsO2-, AsO4(3-), Cd2+, Co2+, CrO4(2-), Cu2+, Hg2+, Ni2+, Pb2+, Sb3+, TeO3(2-), Tl+ and Zn2+. The function of most resistance systems is based on the energy-dependent efflux of toxic ions. Some of the efflux systems are ATPases and others are chemiosmotic cation/proton...

The merC gene of Thiobacillus ferrooxidans was overexpressed in Escherichia coli under the control of the tac promoter. MerC protein synthesized in E. coli has a N-terminal amino acid sequence of S-A-I-X-R-I-I-D-K-I-G-I-V-G-, which agrees with the amino acid sequence deduced from its nucleotide sequence except that an initiating methionine residue...

The arsenical resistance operon of the IncN plasmid R46 consists of 4696 bp and starts with predicted transcriptional control and initiation signals, followed by five genes, arsD, arsA, and arsC. The corresponding Escherichia coli chromosomal ars operon and two staphylococcal ars operons lack arsA and arsD genes. The R46 system contains only the se...

Bacterial plasmids encode resistance systems for toxic metal ions including Ag+, AsO2-, AsO4(3-), Cd2+, CO2+, CrO4(2-), Cu2+, Hg2+, Ni2+, Pb2+, Sb3+, TeO3(2-), Tl+, and Zn2+. In addition to understanding of the molecular genetics and environmental roles of these resistances, studies during the last few years have provided surprises and new biochemi...

Several chromosome- and plasmid-encoded metal resistance genetic systems have been studied in Pseudomonas and related bacteria. Some systems are known with molecular detail whereas others are still poorly understood. The former include resistance genes for cations derived from mercury, cadmium and copper and anions from arsenic and chromium. Except...

The CadC protein from the cadA cadmium resistance operon of Staphylococcus aureus plasmid pI258 regulates transcription of this system in vitro. The CadC protein was overproduced in Escherichia coli cells and partially purified. Gel shift assays of the proposed cadA operator/promoter region DNA showed specific association with the CadC protein. Con...

Microbes are playing increasingly important roles in commercial mining operations, where they are being used in the "bioleaching" of copper, uranium, and gold ores. Direct leaching is when microbial metabolism changes the redox state of the metal being harvested, rendering it more soluble. Indirect leaching includes redox chemistry of other metal c...

Studying metal ion resistance gives us important insights into environmental processes and provides an understanding of basic living processes. This review concentrates on bacterial efflux systems for inorganic metal cations and anions, which have generally been found as resistance systems from bacteria isolated from metal-polluted environments. Th...

Bacterial species have genetically-determined systems for resistances to toxic heavy metals. Those for metals of environmental concern including mercury cadmium, arsenic and others are briefly summarized, considering the genes of the systems and the biochemical mechanisms by which the resistance proteins function.

Arsenic ions, frequently present as environmental pollutants, are very toxic for most microorganisms. Some microbial strains possess genetic determinants that confer resistance. In bacteria, these determinants are often found on plasmids, which has facilitated their study at the molecular level. Bacterial plasmids conferring arsenic resistance enco...

Bacillus isolates from Minamata Bay sediment were selected for the ability to volatilize mercury from a range of organomercurials (including methylmercury). Chromosomal DNA from 74 of 78 such strains hybridized with the mer mercury resistance operon DNA from marine Bacillus sp. strain RC607 (Y. Wang, M. Moore, H. S. Levinson, S. Silver, C. Walsh, a...

Ion homeostasis was undoubtedly one of the earliest attributes of living cells. The maintenance of optimal concentrations of catalytic ions and ionic osmolytes is essential for the conduct of metabolism. Cells, both prokaryotic and eukaryotic, must be especially selective with regard to transition metal ions that cross the cell membranes. Not only...

Bacterial plasmid systems show resistance to toxic metal ions of environmental concern. For many, genes on bacterial plasmids have been identified that encode specific resistance systems for toxic heavy metal ions. These include Ag+, AsO2−, AsO43−, Cd2+, Co2+, CrO42−, Cu2+, Hg2+, Ni2+, Sb3+, TeO32− and Zn2+. A working hypothesis for our laboratory...

Arsenic ions, frequently present as environmental pollutants, are very toxic for most microorganisms. Some microbial strains possess genetic determinants that confer resistance. In bacteria, these determinants are often found on plasmids, which has facilitated their study at the molecular level. Bacterial plasmids conferring arsenic resistance enco...

Bacterial plasmids contain specific genes for resistances to toxic heavy metal ions including Ag+, AsO2-, AsO4(3-), Cd2+, Co2+, CrO4(2-), Cu2+, Hg2+, Ni2+, Pb2+, Sb3+, and Zn2+. Recent progress with plasmid copper-resistance systems in Escherichia coli and Pseudomonas syringae show a system of four gene products, an inner membrane protein (PcoD), a...

Arsenate reductase encoded by Staphylococcus aureus arsenic-resistance plasmid pI258 was overproduced in Escherichia coli and purified. The purified enzyme reduced radioactive arsenate to arsenite when coupled to thioredoxin, thioredoxin reductase, and NADPH. NADPH oxidation coupled to arsenate reduction also required thioredoxin and thioredoxin re...

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A search with the proposed amino acid translation product from the new 'candidate gene' for human Menkes disease against protein sequence libraries showed a remarkable similarity to that for the cadmium efflux ATPase from Staphylococcus aureus resistance plasmids. The Menkes sequence appears closer to the CadA Cd2+ sequence than to P-type ATPases f...

The arsenic resistance operon of Staphylococcus aureus plasmid pI258 determined lowered net cellular uptake of 73As by an active efflux mechanism. Arsenite was exported from the cells; intracellular arsenate was first reduced to arsenite and then transported out of the cells. Resistant cells showed lower accumulation of 73As originating from both a...

pC101, a novel shuttle vector between Escherichia coli and Staphylococcus aureus carrying the lux genes encoding luciferase from Vibrio harveyi, selectable ampicillin and chloramphenicol markers and origins of replication for Gram-negative and Gram-positive bacteria has been constructed. The inducibility of the arsenic and cadmium operon from S. au...

pC101, a novel shuttle vector between Escherichia coli and Straphylococcus aureus carrying the lux genes encoding luciferase from Vibrio harveyi, selectable ampicillin and chloramphenicol markers and origins of replication for Gram-negative and Gram-positive bacteria has been constructed. The inducibility of the arsenic and cadmium operon from S. a...

The plasmid-determined arsenite and antimonite efflux ATPase of bacteria differs from other membrane transport ATPases, which are classified into several families (such as the F0F1-type H(+)-translocating ATP synthases, the related vacuolar H(+)-translocating ATPases, the P-type cation-translocating ATPases, and the superfamily which includes the p...

The arsenic resistance operon of Staphylococcus aureus plasmid pI258 consists of three genes, arsR (encoding the repressor regulatory protein), arsB (the determinant of the membrane efflux protein that confers resistance by pumping arsenic from the cells), and arsC (the small gene whose protein product is required for arsenate resistance only, not...

The arsenic resistance operon from Staphylococcus aureus plasmid pI258 was cloned and sequenced. The DNA sequence contains three genes in the order arsR, arsB, and arsC. The predicted amino acid sequences of the gene products are homologous with those of the products of the ars operons of plasmids pSX267 from Staphylococcus xylosus and R773 from Es...

Regulation of chromosomally determined nutrient cation and anion uptake systems shows important similarities to regulation of plasmid-determined toxic ion resistance systems that mediate the outward transport of deleterious ions. Chromosomally determined transport systems result in accumulation of K+, Mg2+, Fe3+, Mn2+, PO4(3-), SO4(2-), and additio...